GSK’s Depemokimab Cuts Severe Asthma Attacks by Over 50% in Phase III Trials

GSK’s Depemokimab Cuts Severe Asthma Attacks by Over 50% in Phase III Trials

(IN BRIEF) GSK’s depemokimab, a new ultra-long-acting biologic, showed a 54% reduction in severe asthma exacerbations in the SWIFT-1 and SWIFT-2 phase III trials. Administered every six months, it also demonstrated a 72% reduction in hospitalizations and emergency visits, offering a potential breakthrough for managing severe asthma. The drug exhibited a strong safety profile, with no major adverse events. Regulatory approval is anticipated.

(PRESS RELEASE) LONDON, 10-Sep-2024 — /EuropaWire/ — GSK’s new ultra-long-acting biologic, depemokimab, demonstrated significant potential in reducing severe asthma exacerbations, according to the late-breaking data from the SWIFT-1 and SWIFT-2 phase III trials. Presented at the European Respiratory Society International Conference and published in the New England Journal of Medicine, the trials showed a 54% reduction in asthma attacks over a 52-week period compared to placebo in patients with type 2 inflammation-driven asthma.

Depemokimab, which requires only two injections per year, could become a breakthrough treatment in managing severe asthma. The trials revealed a 72% reduction in asthma exacerbations requiring hospitalizations or emergency visits, indicating its strong efficacy.

David Jackson, lead author and respiratory medicine expert, emphasized the importance of preventing asthma exacerbations to avoid long-term lung damage. With sustained suppression of type 2 inflammation, depemokimab may significantly improve outcomes for severe asthma patients.

The trials also indicated a similar safety profile between depemokimab and placebo, with no significant treatment-related adverse events. Regulatory filings are expected, with hopes of approval in the near future.

About the depemokimab development programme

The phase III programme consists of SWIFT-1 and SWIFT-2 in severe asthma, with an open label extension study (AGILE).1,8 SWIFT-1 and SWIFT-2 were replicate 52-week, randomised, double-blind, placebo-controlled, parallel-group, multi-centre clinical trials.1 The trials assessed the efficacy and safety of depemokimab adjunctive therapy in 382 and 380 participants who were randomised to receive depemokimab or a placebo respectively, in addition to their standard of care treatment with medium to high-dose inhaled corticosteroids plus at least one additional controller.1 Number of subjects included in the Full Analysis of SWIFT-1: depemokimab = 250, placebo = 132 and in SWIFT-2: depemokimab = 252, placebo = 128.1

The primary endpoint of reduction in the annualised rate of clinically significant exacerbations (asthma attacks) over 52 weeks vs. placebo for the individual studies were as follows:1

• SWIFT-1: 58% (RR 0.42 [95% CI 0.30, 0.59]; p<0.001)
  • AER = 0.46 annual exacerbation rate in the depemokimab group vs. 1.11 in the placebo group.
• SWIFT-2: 48% (RR 0.52 [95% CI 0.36, 073]; p<0.001)
  • AER = 0.56 annual exacerbation rate in the depemokimab group vs. 1.08 in the placebo group.

An additional study (NIMBLE) is underway to assess the efficacy and safety of depemokimab when participants with severe asthma are switched from mepolizumab or benralizumab.9

Depemokimab’s half-life and high potency for IL-5 means it has the potential to provide sustained inhibition of broad inflammatory functions and is being investigated in a variety of type 2 inflammatory conditions.1,8-13 Depemokimab is currently being evaluated in phase III trials across a range of other IL-5 mediated diseases, including OCEAN for eosinophilic granulomatosis with polyangiitis (EGPA)10, ANCHOR 1 & 2 for chronic rhinosinusitis with nasal polyps (CRSwNP)11,12 and DESTINY for hypereosinophilic syndrome (HES).13

About severe asthma and type 2 inflammation

Severe asthma is defined as asthma that requires treatment with high-dose inhaled corticosteroids plus a second controller (and/or systemic corticosteroids) or biologic therapy, to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite treatment.2 Estimates suggest that severe asthma accounts for more than 60% of all asthma-related costs in some countries, with higher per-patient costs than for a patient with type 2 diabetes or a stroke.14 Patients with severe asthma bear a significant financial burden, for medical care and lost earnings. With some exacerbations leading to sick days or hospitalisation.14 In more than 80% of patients with severe asthma, their condition is driven by type 2 inflammation in which patients exhibit elevated levels of eosinophils (a type of white blood cell).3 Blood eosinophils count can be measured via a simple blood test. IL-5 is a core cytokine (protein) in type 2 inflammation alongside IL-4 and IL-13.2 Type 2 inflammation drives the underlying pathology various immune-mediated conditions. IL-5 is responsible for the growth, activity, and survival of eosinophils.2

About GSK in respiratory

GSK is redefining the future of respiratory medicine as it builds on decades of pioneering work to deliver more ambitious treatment goals and develop the next-generation standard of care, for hundreds of millions of people with respiratory diseases. With an industry-leading respiratory portfolio and pipeline of vaccines, targeted biologics, and inhaled medicines, we are focused on improving outcomes and the lives of people living with all types of asthma and COPD along with less understood diseases like refractory chronic cough or rarer conditions like systemic sclerosis with interstitial lung disease. GSK is harnessing the latest science and technology with the aim to modify underlying disease dysfunction and prevent disease progression.

About GSK

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D “Risk factors” in GSK’s Annual Report on Form 20-F for 2023, and GSK’s Q2 Results for 2024.

References

1. Jackson DJ, et al. Six Monthly Depemokimab in Severe Asthma With an Eosinophilic Phenotype. NEJM. Published on September 9 at NEJM.org
2. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention,2024. Updated May 2024. Available at: https://ginasthma.org/. Accessed May 2024.Buchheit KM, et al. Mepolizumab targets multiple immune cells in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2021;148(2):574-584.
3. Heaney L, et al. Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort. Chest. 2021;160(3):814-830.
4. Barretto KT, et al. Human airway epithelial cells express a functional IL-5 receptor. Allergy. 2020;75(8):2127-2130.
5. Bajbouj K, et al. IL-5 receptor expression in lung fibroblasts: Potential role in airway remodelling in asthma. Allergy. 2023;78(3):882-885.
6. Siddiqui S, et al. Eosinophils and tissue remodeling: Relevance to airway disease. J Allergy Clin Immunol. 2023;152(4):841-857.
7. Bergantini L, et al. Regulatory T cell monitoring in severe eosinophilic asthma patients treated with mepolizumab. Scand J Immunol. 2021;94(1):e13031.
8. ClinicalTrials.gov. An Open-Label Extension Study of GSK3511294 (Depemokimab) in Participants Who Were Previously Enrolled in 206713 (NCT04719832) or 213744 (NCT04718103) (AGILE). Available at: https://clinicaltrials.gov/study/NCT05243680 Last accessed May 2024.
9. ClinicalTrials.gov. A Study of GSK3511294 (Depemokimab) Compared With Mepolizumab or Benralizumab in Participants With Severe Asthma With an Eosinophilic Phenotype (NIMBLE). Available at: https://clinicaltrials.gov/study/NCT04718389 Accessed May 2024.
10. ClinicalTrials.gov. Efficacy and Safety of Depemokimab Compared With Mepolizumab in Adults With Relapsing or Refractory Eosinophilic Granulomatosis With Polyangiitis (EGPA) Available at: https://clinicaltrials.gov/study/NCT05263934 Accessed May 2024.
11. ClinicalTrials.gov. Efficacy and Safety of Depemokimab (GSK3511294) in Participants With Chronic Rhinosinusitis With Nasal Polyps (ANCHOR-1) Available at: https://clinicaltrials.gov/study/NCT05274750 Accessed May 2024
12. ClinicalTrials.gov. Efficacy and Safety of Depemokimab (GSK3511294) in Participants With Chronic Rhinosinusitis With Nasal Polyps (ANCHOR-2) Available at: https://clinicaltrials.gov/study/NCT05281523 Accessed May 2024.
13. ClinicalTrials.gov. Depemokimab in Participants With Hypereosinophilic Syndrome, Efficacy, and Safety Trial (DESTINY) Available at: https://clinicaltrials.gov/study/NCT05334368 Accessed May 2024.
14. Israel, E, et al. Severe and Difficult-to-Treat Asthma in Adults. N Engl J Med 2017;377:965-76.

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SOURCE: GlaxoSmithKline plc